Author

Date of Award

Document Type

Degree Name

Administrative Home Department

Department of Biological Sciences

Advisor 1

Xiaoqing Tang

Committee Member 1

Guiliang Tang

Committee Member 2

Chandrashekhar P. Joshi

Committee Member 3

Zhiying Shan

Abstract

Diabetes mellitus is a disease associated with impaired glucose homeostasis leading to chronic hyperglycemia (elevated blood glucose level). Insulin and Glucagon, hormones secreted from pancreatic beta and alpha cells respectively play a vital role in balancing the normal blood glucose level. We have identified a microRNA (small non-coding regulatory RNA), miR-483 to be highly expressed in pancreatic beta cells when compared to alpha cells and more interestingly high glucose conditions further augmented its expression level. In this study, we have 1) demonstrated some important roles of miR-483 in regulating the functions of pancreatic beta and alpha cells by targeting SOCS3 (suppressor of cytokine signaling 3)-its working partner, 2) investigated the role of Krüppel-like Factor 2 (KLF2) in regulating miR-483 expression in pancreatic beta cells, 3) revealed some other potential targets of miR-483 by HiSeq RNA sequencing after silencing miR-483 expression in pancreatic beta cells and 4) analyzed physiological functions of miR-483 in vivo under normal and high fat diet conditions using a pancreatic beta cell specific miR-483 knockout mouse model. Taken together, our results indicate that miR-483 has important roles in both regulating and protecting the functions of pancreatic alpha and beta cells. Thus, with more studies, we strongly believe that miR-483 can be used as a potential therapeutic agent for the treatment of diabetes mellitus.